254 research outputs found
Cardiac adaptations from 4 weeks of intensity-controlled vigorous exercise are lost after a similar period of detraining
Intensityâcontrolled (relative to VO2max) treadmill exercise training in adult rats results in the activation and ensuing differentiation of endogenous câkitpos cardiac stem/progenitor cells (eCSCs) into newly formed cardiomyocytes and capillaries. Whether these trainingâinduced adaptations persist following detraining is undetermined. Twelve male Wistar rats (~230 g) were exercised at 80â85% of their VO2max for 30 min dayâ1, 4 days weekâ1 for 4 weeks (TR; n = 6), followed by 4 weeks of detraining (DTR; n = 6). Twelve untrained rats acted as controls (CTRL). Exercise training significantly enhanced VO2max (11.34 mL kgâ1 minâ1) and wet heart weight (29%) above CTRL (P < 0.05). Echocardiography revealed that exercise training increased LV mass (~32%), posterior and septal wall thickness (~15%), ejection fraction and fractional shortening (~10%) compared to CTRL (P < 0.05). Cardiomyocyte diameter (17.9 ± 0.1 ÎŒm vs. 14.9 ± 0.6 ÎŒm), newly formed (BrdUpos/Ki67pos) cardiomyocytes (7.2 ± 1.3%/1.9 ± 0.7% vs. 0.2 ± 0.1%/0.1 ± 0.1%), total cardiomyocyte number (45.6 ± 0.6 Ă 106 vs. 42.5 ± 0.4 Ă 106), câkitpos eCSC number (884 ± 112 per 106 cardiomyocytes vs. 482 ± 132 per 106 cardiomyocytes), and capillary density (4123 ± 227 per mm2 vs. 2117 ± 118 per mm2) were significantly greater in the LV of trained animals (P < 0.05) than CTRL. Detraining removed the stimulus for câkitpos eCSC activation (640 ± 98 per 106 cardiomyocytes) and resultant cardiomyocyte hyperplasia (0.4 ± 0.3% BrdUpos/0.2 ± 0.2% Ki67pos cardiomyocytes). Capillary density (3673 ± 374 per mm2) and total myocyte number (44.7 ± 0.5 Ă 106) remained elevated following detraining, but cardiomyocyte hypertrophy (15.0 ± 0.4 ÎŒm) was lost, resulting in a reduction of anatomical (wall thickness ~4%; LV mass ~10% and cardiac mass ~8%, above CTRL) and functional (EF & FS ~2% above CTRL) parameters gained through exercise training. These findings demonstrate that cardiac adaptations, produced by 4 weeks of intensityâcontrolled exercise training are lost after a similar period of detraining
Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy
It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes
Cloning and characterization of mammalian myosin regulatory light chain (RLC) cDNA: the RLC gene is expressed in smooth, sarcomeric, and nonmuscle tissues.
The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation
Aims It is a dogma of cardiovascular pathophysiology that the increased cardiac mass in response to increased workload is produced by the hypertrophy of the pre-existing myocytes. The role, if any, of adult-resident endogenous cardiac stem/progenitor cells (eCSCs) and new cardiomyocyte formation in physiological cardiac remodelling remains unexplored. Methods and results In response to regular, intensity-controlled exercise training, adult rats respond with hypertrophy of the pre-existing myocytes. In addition, a significant number (âŒ7%) of smaller newly formed BrdU-positive cardiomyocytes are produced by the exercised animals. Capillary density significantly increased in exercised animals, balancing cardiomyogenesis with neo-angiogenesis. c-kitpos eCSCs increased their number and activated state in exercising vs. sedentary animals. c-kitpos eCSCs in exercised hearts showed an increased expression of transcription factors, indicative of their commitment to either the cardiomyocyte (Nkx2.5pos) or capillary (Ets-1pos) lineages. These adaptations were dependent on exercise duration and intensity. Insulin-like growth factor-1, transforming growth factor-ÎČ1, neuregulin-1, bone morphogenetic protein-10, and periostin were significantly up-regulated in cardiomyocytes of exercised vs. sedentary animals. These factors differentially stimulated c-kitpos eCSC proliferation and commitment in vitro, pointing to a similar role in vivo. Conclusion Intensity-controlled exercise training initiates myocardial remodelling through increased cardiomyocyte growth factor expression leading to cardiomyocyte hypertrophy and to activation and ensuing differentiation of c-kitpos eCSCs. This leads to the generation of new myocardial cells. These findings highlight the endogenous regenerative capacity of the adult heart, represented by the eCSCs, and the fact that the physiological cardiac adaptation to exercise stress is a combination of cardiomyocyte hypertrophy and hyperplasia (cardiomyocytes and capillaries)
P365Protection against doxorubicine-induced cardiomyopathy by bergamot polyphenols through myocyte survival and cardiac stem cell activation
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Co-expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature.
Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion.
Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells (PICs) Enhance Endogenous Repair of Injured Porcine Skeletal Muscle
Skeletal muscle-derived PW1pos/Pax7neg interstitial cells (PICs) express and secrete a multitude of proregenerative growth factors and cytokines. Utilizing a porcine preclinical skeletal muscle injury model, delivery of allogeneic porcine PICs (pPICs) significantly improved and accelerated myofiber regeneration and neocapillarization, compared with saline vehicle control-treated muscles. Allogeneic pPICs did not contribute to new myofibers or capillaries and were eliminated by the host immune system. In conclusion, allogeneic pPIC transplantation stimulated the endogenous stem cell pool to bring about enhanced autologous skeletal muscle repair and regeneration. This allogeneic cell approach is considered a cost-effective, easy to apply, and readily available regenerative therapeutic strategy
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